Purpose: :
We have identified the K42E mutation in DHDDS (dehydrodolicholdiphosphate synthase) as the cause of retinitis pigmentosa (RP)phenotype in a single family with non-syndromic recessive RP.The present work examines whether insufficient DHDDS activityinduces photoreceptor degeneration in zebrafish.

Methods: :
Morpholino oligonucleotides (MO) designed against exon1/intron1of the zebrafish DHDDS gene were injected into fertilized eggs.Embryos were allowed to develop for four days. Wild type andDHDDS morphants were tested for responses to light on-off switcheswith a high-speed camera recording at 60 frames per second.After behavioral analysis, semi-thin plastic sections of fisheyes were prepared and examined by light microscopy. Cone outersegments were labeled by PNA (peanut agglutinin) and examinedby confocal microscopy.

Conclusions: :
Our findings are consistent with DHDDS being a key protein forthe generation and continuous renewal of photoreceptor outersegments. DHDDS catalyzes the formation of dehydrodolichol diphasphateas the first step of biosynthesis of dolichol, the criticallipid carrier in the dolichol pathway for N-linked glycosylation.Insufficient DHDDS activity would affect the efficiency of proteinglycosylation. Photoreceptors produce large amount of glycoproteinopsin or rhodopsin each day to renew outer segments. Our resultsthus highlight the importance of protein glycosylation in photoreceptorouter segment generation and renewal and support the notionthat deficiency in protein glycosylation can result in retinaldegeneration. Additional experiments are in progress to characterizechanges in photoreceptors in the DHDDS knock-out and DHDDS K42Eknock-in mice.